ENST00000645242.1:n.274+6544A>G

Variant names:

• chr8-11493711-A-G
• rs1382568
• ENST00000645242.1:n.274+6544A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000645242.1(BLK):​n.274+6544A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,854 control chromosomes in the GnomAD database, including 14,998 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (14998 hom., cov: 31)
• Consequence: BLK ENST00000645242.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 19 publications found

Genes affected

BLK (HGNC:1057): (BLK proto-oncogene, Src family tyrosine kinase) This gene encodes a nonreceptor tyrosine-kinase of the src family of proto-oncogenes that are typically involved in cell proliferation and differentiation. The protein has a role in B-cell receptor signaling and B-cell development. The protein also stimulates insulin synthesis and secretion in response to glucose and enhances the expression of several pancreatic beta-cell transcription factors. [provided by RefSeq, Aug 2010]

BLK Gene-Disease associations (from GenCC):

• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• maturity-onset diabetes of the young type 11

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• monogenic diabetes

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLK	ENST00000645242.1	n.274+6544A>G		intron_variant	Intron 1 of 11
BLK	ENST00000696154.2	n.274+6544A>G		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64298 AN: 151736 Hom.: 14999 Cov.: 31

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.00505

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.432

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.424 AC: 64311 AN: 151854 Hom.: 14998 Cov.: 31 AF XY: 0.412 AC XY: 30581 AN XY: 74212

African (AFR) AF: 0.323 AC: 13363 AN: 41344

American (AMR) AF: 0.330 AC: 5049 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1977 AN: 3472

East Asian (EAS) AF: 0.00506 AC: 26 AN: 5136

South Asian (SAS) AF: 0.369 AC: 1772 AN: 4800

European-Finnish (FIN) AF: 0.393 AC: 4137 AN: 10538

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36614 AN: 67962

Other (OTH) AF: 0.427 AC: 898 AN: 2102

Alfa AF: 0.0511 Hom.: 14263

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.38
DANN	Benign	0.71
PhyloP100		-0.096

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1382568; hg19: chr8-11351220;